These authors contributed equally to this work.
Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer-binding protein β activation
Article first published online: 30 MAY 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 5, pages 797–809, May 2012
How to Cite
Han, E. H., Kim, H. G., Choi, J. H., Jang, Y.-J., Lee, S. S., Kwon, K.-i., Kim, E., Noh, K., Jeong, T. C., Hwang, Y. P., Chung, Y. C., Kang, W. and Jeong, H. G. (2012), Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer-binding protein β activation. Mol. Nutr. Food Res., 56: 797–809. doi: 10.1002/mnfr.201100697
Additional Corresponding Author: Dr. Wonku Kang Email: email@example.com
- Issue published online: 30 MAY 2012
- Article first published online: 30 MAY 2012
- Manuscript Accepted: 16 JAN 2012
- Manuscript Revised: 13 JAN 2012
- Manuscript Received: 17 OCT 2011
- National Research Foundation of Korea (NRF). Grant Numbers: 2009–0093815, 2010–00266220
- Food–drug interactions;
Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the principal pungent ingredient in hot red and chili peppers. Many studies have focused on the anticarcinogenic or chemopreventive activities of capsaicin. However, the influence of capsaicin on CYP3A4, its involvement in drug metabolism, and the underlying mechanisms remain unclear.
Methods and results
Here, we examined the effect of capsaicin on CYP3A4 expression and the metabolism of CYP3A1 substrate, nifedipine in male Sprague–Dawley rats. Capsaicin induced the enzymatic activity and expression of CYP3A4 in HepG2 cells. Treatment with a human pregnane X receptor (hPXR) inhibitor reduced the inductive effects of capsaicin on CYP3A4 expression. Capsaicin also induced the activation of CCAAT/enhancer-binding protein β (C/EBPβ). Moreover, capsaicin increased the activation of the transient receptor potential vanilloid type-1 receptor downstream signaling components Ca2+/calmodulin-dependent protein kinase and Akt. Capsaicin elevated the level of CYP3A1 in rat liver and significantly increased the biotransformation of nifedipine to dehydronifedipine.
From these data, we conclude that capsaicin induces CYP3A4 expression in vitro and in vivo. This induction was achieved by the activation of hPXR and C/EBPβ. Our results suggest that capsaicin might induce CYP3A4 expression; thus, exposure to capsaicin may increase the metabolism of CYP3A4 substrate and potentially cause food–drug interactions.